Recentstudiesusinghigh-speedfMRItechniqueshavedetectedrestingstateconnectivityatfrequenciesup to 5 Hz in the visual and the motor cortices with significantly higher spatial-temporal stability than the correspondinglowfrequency(<0.1Hz)restingstateconnectivity.Thisapproachhasthepotentialforaddressing principallimitationsofmappinglowfrequencyrestingstateconnectivity,suchashighsensitivitytosignaldrifts and long time scales necessary for separating major RSNs. However, other studies using lower temporal resolution have been more cautious regarding the possible signal sources or were unable to replicate the findings.Noneofthepublishedstudieshaveidentifiedabiophysicalmechanism. We have recently detected remarkably strong high frequency connectivity in the auditory cortex, both in healthycontrolsandinpatientswithbraintumors,withsensitivityandspatialspecificitythatapproachesthatof conventionallowfrequencyrestingstateconnectivity,usinghigh-speedmulti-slabecho-volumarimaging(MEVI) (136 ms temporal resolution) and a confound-tolerant seed-based sliding window correlation analysis. Our preliminary data also show high frequency connectivity across several other major RSNs, consistent with previousstudies.Wehypothesizethathighfrequencyconnectivitymayreflectfastcerebrovascularregulation. Thiscontrastmechanismwouldenablenovelclinicalapplicationsthatarenotfeasiblewithcurrentmethodology, suchasimprovedlocalizationofdeepsourcesofinter-ictalepileptogenicactivitytoguidesurgicalresectionand mappingofdisease-relatedabnormalitiesinvascularcompliance. Thespecificaimsofthisstudyare: (1)Characterize the biophysical mechanisms of high frequency connectivity in healthy controls. We will compare2D-acceleratedMEVIwith68msTRandmulti-bandEPIwith136msTRin12healthycontrols at3Tesla.BiophysicalmodelingbasedonarterialspinlabelingwillbeusedforcalibratedfMRI.Filtering of cardiac pulsatility up to the 3rd harmonic will minimize blood vessel contamination. The detection thresholdforhighfrequencyconnectivitywillbedeterminedbysimulatingcorrelationsinaRiciannoise model. (2)Characterizethephysiologicalbasisandclinicalpotentialofhigh-frequencyconnectivityinpatientswith braintumors.Wewillassessthephysiologicalbasisofhigh-frequencyconnectivityin10patientswith braintumorsadjacenttotheauditoryandsensorimotorcortexbymappinglesion-relateddisplacementof connectivity. We will then compare sensitivity and specificity with task-based fMRI mapping and intra-operativeelectrocorticography. Ifsuccessful,thisresearchwillenablemappingofneuralactivityandconnectivityatmuchshortertimescales thancurrentlyfeasible,thusimprovingthecharacterizationofthetemporaldynamicsoffunctionalconnectivity, enhancing the spatial-temporal information obtained from combining fMRI with EEG and MEG and informing about the neurophysiological mechanisms that control brain connectivity and neurovascular coupling. The improved tolerance to slowly varying confounding signals and head movement will have considerable clinical impactforinvestigatingdifficulttoimagepopulations,suchasepilepsy,stroke,Parkinson?sdiseaseandvascular disease.